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Review
. 2023 Dec 13:14:1323560.
doi: 10.3389/fimmu.2023.1323560. eCollection 2023.

Roles and functions of IAV proteins in host immune evasion

Farooq Rashid  1   2   3 , Zhixun Xie  1   2   3 , Meng Li  1   2   3 , Zhiqin Xie  1   2   3 , Sisi Luo  1   2   3 , Liji Xie  1   2   3
Affiliations
Review

Roles and functions of IAV proteins in host immune evasion

Farooq Rashid et al. Front Immunol. .

Abstract

Influenza A viruses (IAVs) evade the immune system of the host by several regulatory mechanisms. Their genomes consist of eight single-stranded segments, including nonstructural proteins (NS), basic polymerase 1 (PB1), basic polymerase 2 (PB2), hemagglutinin (HA), acidic polymerase (PA), matrix (M), neuraminidase (NA), and nucleoprotein (NP). Some of these proteins are known to suppress host immune responses. In this review, we discuss the roles, functions and underlying strategies adopted by IAV proteins to escape the host immune system by targeting different proteins in the interferon (IFN) signaling pathway, such as tripartite motif containing 25 (TRIM25), inhibitor of nuclear factor κB kinase (IKK), mitochondrial antiviral signaling protein (MAVS), Janus kinase 1 (JAK1), type I interferon receptor (IFNAR1), interferon regulatory factor 3 (IRF3), IRF7, and nuclear factor-κB (NF-κB). To date, the IAV proteins NS1, NS2, PB1, PB1-F2, PB2, HA, and PA have been well studied in terms of their roles in evading the host immune system. However, the detailed mechanisms of NS3, PB1-N40, PA-N155, PA-N182, PA-X, M42, NA, and NP have not been well studied with respect to their roles in immune evasion. Moreover, we also highlight the future perspectives of research on IAV proteins.

Keywords: IAV proteins; IAVs; IFNs; host immune system; immune evasion.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
IFN signaling pathway activation and evasion by IAV proteins. The viral genome is recognized by RIG-I and MDA5. IRF3, IRF7, and NF-κB trigger the production of IFNs. IFNs are secreted to induce the JAK/STAT pathway, which express ISGs. Different IAV proteins antagonize different proteins in the host innate immune signaling pathway. NS1 binds with IKK, RIG-I, and TRIM25 to escape the host immune system, NS2 interacts with IRF7 to suppress its nuclear translocation, the PB1 protein interacts with and degrades MAVS, and PB1-F2 probably interacts with MAVS to inhibit IFN production (dotted lines indicate that the interaction between these two proteins has not yet been confirmed). PB1-F2 also binds with IKKβ to suppress NF-κB signaling. The HA protein degrades IFNAR1, and PA binds with and inhibits the nuclear translocation of IRF3. The dotted arrow indicates that the interaction between the proteins has not yet been confirmed. The figure was created with BioRender.com.
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Publication types

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The project was funded by grants from the Guangxi Science and Technology Project (No. AB21076004), the Guangxi Science Base and Talents Special Program (AD17195083), and the Guangxi BaGui Scholars Program Foundation (2019A50).